Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia.

Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.

Malignancy-Associated Secondary Hemophagocytic Lymphohistiocytosis Mimicking an Infection: A Case Report and Review of the Literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening hematological disorder of immune dysregulation associated with significant challenges in diagnosis and management. Described as primary HLH secondary to genetic defects or more commonly secondary to infections, it can also occur secondary to malignancy, i.e., malignancy-associated hemophagocytic lymphohistiocytosis (M-HLH). A five-year-old male child presented with left cervical adenopathy and a high-spiking fever for two weeks. He had pallor, anasarca, multiple enlarged and matted cervical lymph nodes, respiratory distress, and hepatomegaly. He had continuous high-grade fever spikes (maximum 105 °F), not touching baseline despite broad-spectrum antibiotics. The CBC revealed anemia with thrombocytopenia. Liver function tests showed mild transaminitis and hypoalbuminemia. The HLH workup showed elevated ferritin, low fibrinogen, and elevated triglycerides. Lymph node biopsy showed intermediate to large atypical monomorphic lymphocyte cells with ALK, CD30, CD5, CD3, CD45, and BCL-2 (weak positive) positivity and Ki-67-95%, suggestive of anaplastic large cell lymphoma (ALCL). The bone marrow aspiration showed reactive marrow with hemophagocytosis. The patient was started on dexamethasone and chemotherapy per the Children's Oncology Group's (COG) ALCL protocol. He showed remarkable clinical improvement and went into remission after the induction phase. Malignancy associated with HLH can mimic infection, as in our patient with high-spiking fever, consolidation, and mediastinal adenopathy. A high index of suspicion is necessary to arrive at an appropriate, early diagnosis, and workup for malignancy is to be considered when an infectious etiology is not identified after thorough evaluation.

Nephrotic Syndrome and Hodgkins Lymphoma - an Unusual Association.

Background: An association between nephrotic syndrome and extrarenal neoplasia was described for the first time in 1922. The reported incidence of nephrotic syndrome in Hodgkin lymphoma is less than 1%. Clinical description: We present a 13 year old boy who was admitted with complaints of abdominal pain, vomiting and loose stools for 2 months. He had a history of significant weight loss of 5kg in a couple of months.On examination, he had bilateral pedal oedema and right cervical lymphadenopathy. Cervical lymph node biopsy revealed nodular sclerosis type of Hodgkin lymphoma. He also had hypoalbuminemia, massive proteinuria and hypercholesterolemia.Secondary nephrotic syndrome due to Hodgkin's lymphoma was made as a clinical diagnosis. Management and outcome: He had been started on chemotherapy (with Prednisolone, Vincristine, Doxorubicin, Etoposide) for stage 3B Hodgkin lymphoma. He tolerated the chemotherapy well. Though he had symptomatic edema, managed conservatively as the urine output was adequate. On follow up, he attained spontaneous remission of nephrotic syndrome. Conclusion: Overt proteinuria might be the manifestation of paraneoplastic syndrome in children with Hodgkin lymphoma and with the management of the primary disease, proteinuria resolves spontaneously.

Detection of Human Leukocyte Antigen B27 by Flowcytometry in Patients With Suspected Ankylosing Spondylitis in a Tertiary Care Centre.

Introduction Human leukocyte antigen B27 (HLA-B27) is strongly implicated in the pathogenesis of ankylosing spondylitis (AS). Hence, HLA-B27 testing is routinely used in the diagnosis of AS. Objectives We aimed to establish the frequency of HLA-B27 in AS patients by flow cytometry and relate the differences between B27+ and B27- cases to the serum concentrations of rheumatoid arthritis factor (RA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Methods  The study population included a total of 210 patients who visited the tertiary health care center. The peripheral blood samples obtained from AS patients were subjected to a qualitative two-color direct immunofluorescence method using the HLA-B27/CD3 antibody for the rapid detection of HLA-B27 antigen expression in erythrocyte-lysed whole blood in FACSCalibur flow cytometer (Becton Dickinson, USA). Results Out of 210 AS patients, the distribution of HLA-B27 positivity was observed only in 46 (22%) patients. The remaining 164 patients (78.1%) were negative for HLA-B27. Of the 46 HLA positive patients, 39 (25.34%) were males and only seven (12.5%) were females. In both sexes, HLA-B27 frequency was significantly higher in the age group 21-30 years, followed by 41-50 years. The current study also revealed a significant association between sex and age of onset of HLA­B27 detection in patients with suspected AS. Disease activity was not significantly correlated with RA, ESR, and CRP. Conclusions The detection of HLA-B27 by flow cytometry proved to be a reliable test in the screening of AS in the Indian population.

A Journey Across Oceans With a Heavy Heart: Rare Presentation of a Pediatric Malignancy.

Myeloid sarcoma, due to extramedullary deposition of myeloblasts, is one of the rare presentations in acute myeloid leukemia. We present an extremely rare case of a 5-year-old boy with cardiac myeloid sarcoma. Noninvasive mode of diagnosis, timely initiation of chemotherapy and meticulous supportive care are the keys to successful outcome. (Level of Difficulty: Intermediate.).

Dynamic Profile of Prognostic Hematologic Indicators in Patient Under Intensive Care for COVID-19 Disease: A One-Year Study at a Tertiary Care Centre in South India.

Introduction Viral pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS COV-2) releases cytokines which result in neutrophils migration to the bloodstream and cytotoxic effect on lymphocytes. The ongoing pathology is reflected in the derangement of blood cells and the variations and calculations based on them that help in assessing the severity of the disease and prognosis. Aim This study aimed to compare the differences in the dynamic changes of the blood cells among survivors and non-survivors of COVID-19 disease so that cut-offs can be arrived at to aid triage at the intensive care unit (ICU) and to predict mortality.  Material and methods A one-year study was conducted on patients hospitalized in the ICU. The demography and laboratory values of neutrophils and lymphocytes in percentages and absolute values, and platelet count in numbers were retrieved for eight consecutive values. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) was calculated from absolute counts. Statistical analysis was done using the Chi-Square test and Mann-Whitney test and a P-value of <0.05 is considered significant. The comparison was done between survivors and non-survivors. Result Among the 3142 patients admitted for COVID-19 disease, 7.6% required ICU care of whom 65.5% survived and 35.5% succumbed to the illness. Survivors were younger and comparable between both sexes. Though both groups had an ascending trend of neutrophils, lymphocytes, NLR, and PLR, the baseline characteristics were significantly lower in those who survived on a day-to-day basis. Neutrophilia above 80%, NLR 7.96, PLR 200 predicted the need for admission in ICU. Neutrophilia of 87% and lymphopenia of 10% were associated with adverse outcomes (mortality). Mortality can be predicted when neutrophil rises above 93% or lymphocytes fall below 5.2%. An initial NLR of 7.96 and PLR of 160 as well as peak NLR of 12.29 and peak PLR 400 predict mortality. Conclusion Serial blood counts are essential for hospitalized patients with COVID-19 for early triaging, and to assess severity and prognosis. The NLR of 6.7 and PLR of 160 require intensive care. The dynamic increase of NLR and PLR show worsening of the disease process and NLR of 40.95 and PLR of 400 predict mortality.